UMIN-CTR Clinical Trial

Basic information
Public title	AFIRE Study: Atrial Fibrillation and Ischemic events with Rivaroxaban in patiEnts with stable coronary artery disease Study
Acronym	AFIRE Study
Scientific Title	AFIRE Study: Atrial Fibrillation and Ischemic events with Rivaroxaban in patiEnts with stable coronary artery disease Study
Scientific Title:Acronym	AFIRE Study
Region	Japan

Condition
Condition	Non-valvular atrial fibrillation
Classification by specialty	Cardiology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the efficacy and safety of rivaroxaban monotherapy compared to rivaroxaban in co-administration with a single anti-platelet therapy in non-valvular atrial fibrillation patients with stable coronary artery diseases. For the efficasy of rivaroxaban monotherapy, for the composite endpoint incidence of cardiovascular events or all-cause mortality for the rivaroxaban and anti-platelet drugs single agent combination therapy to verify the non-inferiority. for safety, to verify the superiority for serious bleeding complications incidence.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	(1)Primary efficacy endpoints Composite endpoint of cardiovascular events (stroke, non-CNS embolism, myocardial infarction, unstable angina pectoris requiring revascularizations or all-cause mortality) (2)Safety primary endpoints Major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH)
Key secondary outcomes	1)Net adverse clinical and cerebral events (NACCE) (net clinical benefit) All-cause death, myocardial infarction, stroke and major bleeding 2)Ischemic cardiovascular events and death (1)All-cause mortality (2)Cardiovascular death (3)Non-cardiovascular death (4)Myocardial infarction (5)Unstable angina pectoris requiring revascularization (6)Ischemic stroke (7)Transient ischemic attack (8)Systemic embolism (9)PCI/CABG (10)Stent thrombosis (11)Ischemic stroke and systemic embolism 3)Any bleeding 4)Adverse events excluding hemorrhagic events 5)Comparison of the primary endpoints between patients treated with aspirin and treated with thienopyridine derivatives 6)Stratified analysis of the primary endpoints, ischemic cardiovascular events and mortality according to the CHADS2 score and CHA2DS2-VASc score 7)Stratified analysis of the incidences of the primary endpoints, ischemic cardiovascular events and mortality according to subject characteristics 8)Stratified analysis of major bleeding and all bleeding events in patients treated concomitantly with any antiplatelet and patients not treated with any antiplatelet according to the HAS-BLED score and analysis of specificity and sensitivity 9)Comparison of the incidence of bleeding events according to whether or not proton pump inhibitors (PPIs) are used 10)Comparison of the incidences of the primary endpoints according to whether rivaroxaban is administered in the morning or evening 11)Investigation of relationships between ischemic cardiovascular events, bleeding events/adverse events and discontinuation of treatment with antithrombotic agents 12)Investigation of relationships between prothrombin time at trough and bleeding events and the cutoff values according to whether or not antiplatelet drugs are concomitantly used 13)The incidence of the primary endpoints according to adherence

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Central registration

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Rivaroxaban monotherapy Rivaroxaban will be orally administered at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min until end of study.
Interventions/Control_2	Rivaroxaban co-administered with single anti-platelet therapy Rivaroxaban and a single antiplatelet will be orally administered until end of study. Antiplatelet will be selected from aspirin or thienopyridine derivatives (clopidogrel or prasugrel). Rivaroxaban administration: Rivaroxaban will be orally administered after a meal at a dose of 15 mg if the creatinine clearance (CLcr) is 50 mL/min or more and at a dose of 10 mg if the CLcr is 15-49 mL/min (regardless of time). Aspirin administration: Aspirin will be orally administered once a day at a dose of 81 mg or 100 mg. Clopidogrel administration: Clopidogrel will be orally administered once a day after a meal at a dose of 75 mg. The dose will be reduced to 50mg once a day by consideration for aging, body weight or clinical findings. Prasugrel administration: Prasugrel will be orally administered once a day at a dose of 3.75 mg. If the body weight is 50kg or less than 50kg, the dose will be considered to reduce to 2.5 mg once a daily by evaluation for aging, renal function or other bleeding risk and thrombotic risk.
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
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Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients with non-valvular atrial fibrillation complicated with stable coronary artery disease who are 20 years or more at the obtaining of informed consent, CHADS2 score are 1 or more, and fulfil the criteria below and can provide written consent for participation in the present study will be eligible. 1) Patients who underwent percutaneous coronary intervention, including plain old balloon angioplasty, at least one year ago 2) Patients who have coronary stenosis requiring no percutaneous coronary intervention (50% or more stenosis) as indicated by coronary CT or coronary angiography 3) Patients who underwent coronary artery bypass graft CABG at least one year ago
Key exclusion criteria	1)Patients who are contraindicated for rivaroxaban 2)Patients who are contraindicated for aspirin, thienopyridine derivatives (clopidogrel or prasugrel) 3)Patients who underwent PCI, including POBA, in the past one year 4)Patients who are going to undergo revascularization 5)Patients who have a past history of stent thrombosis 6)Those who are going to undergo invasive surgery (excluding digestive endoscopy and biopsy) 7)Patients who have active tumors 8)Patients who have poorly-controlled hypertension (systolic blood pressure at hospital admission based on two or more measurements: 160 mmHg or more) 9)Patients who cannot discontinue treatment with antiplatelet drugs (the physician in charge will make a decision on the basis of the lesion shape, lesion site and type of stents.) (10)Patients judged as inappropriate for this study by investigators Contraindicated for rivaroxaban (1)Unstable CAD (2)Patients with a past history of stent thrombosis (3)Patients judged as inappropriate for this study by investigators
Target sample size	2200

Research contact person
Name of lead principal investigator	1st name Middle name Last name Satoshi yasuda
Organization	Japan Cardiovascular Research Foundaition
Division name	National Cerebral and Cardiovascular Center
Zip code
Address	5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
TEL	+81-6-6872-0010
Email	afire@jcvrf.jp

Public contact
Name of contact person	1st name Middle name Last name Saburo Saito
Organization	Japan Cardiovascular Research Foundation
Division name	Administration Office
Zip code
Address	5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan
TEL	06-6872-0010
Homepage URL
Email	afire@jcvrf.jp

Sponsor
Institute	Japan Cardiovascular Research Foundation
Institute
Department

Funding Source
Organization	Bayer Yakuhin , Ltd
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
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IRB Contact (For public release)
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Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	独立行政法人 国立循環器病研究センター（大阪府） 熊本大学医学部附属病院（熊本県） 大阪医科大学（大阪府）

Other administrative information
Date of disclosure of the study information	2015 Year 02 Month 23 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
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Results
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Baseline Characteristics
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Progress
Recruitment status	Terminated
Date of protocol fixation	2014 Year 12 Month 26 Day
Date of IRB	2014 Year 12 Month 19 Day
Anticipated trial start date	2015 Year 01 Month 01 Day
Last follow-up date	2018 Year 09 Month 30 Day
Date of closure to data entry
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Other
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Management information
Registered date	2015 Year 02 Month 23 Day
Last modified on	2019 Year 03 Month 27 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019280

Research Plan
Registered date	File name

Research case data specifications
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Research case data
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